synthetase

Synthetase is a term used for enzymes that catalyze the formation of a chemical bond in a substrate with the input of energy, typically from ATP or GTP. In many contexts, synthetases are a subset of ligases (enzyme class EC 6) that join two substrates while hydrolyzing a nucleotide triphosphate to drive the reaction. The name is often contrasted with synthases, which catalyze bond formation without direct nucleotide hydrolysis.

A prominent group is aminoacyl-tRNA synthetases (aaRS), which attach amino acids to their cognate transfer RNAs as the first step of protein synthesis. Activation of the amino acid occurs as aminoacyl-AMP, followed by transfer to tRNA. Some aaRS enzymes include editing domains to correct mischarging and help maintain fidelity during translation.

Other synthetases include acetyl-CoA synthetase and various acyl-, amino-, and nucleotide-synthetases that form thioester, amide, or ester bonds by using ATP or related nucleotides. They play central roles in metabolism and cellular regulation, and some participate in pathways beyond amino acid activation, depending on the substrates and products involved.

Defects or inhibitors of synthetases have clinical relevance. For example, certain antibiotics target bacterial aminoacyl-tRNA synthetases, disrupting protein synthesis. While the term synthetase is sometimes used loosely, it generally denotes enzymes that catalyze bond formation with concomitant nucleotide triphosphate hydrolysis, effectively coupling synthesis to energy consumption. See also ligase and synthase for related enzyme categories.